Many gene silencing technologies have focused on targeting mRNA using ribozymes, DNAzymes, complementary RNA or DNA oligonucleotides. It is attractive that mRNA is accessible during transcription, processing (e.g., 5′-capping, intro-exon splicing, polyadenylation, nuclear export), and ribosomal binding and translation. Hybridization of an ‘antisense’ oligodeoxynucleotide (asODN) to a target mRNA inhibits translation by sterically blocking the ribosome and/or recruiting endogenous ribonucleases. In mammalian cells, mRNA/asODN duplex formation activates RNase H-mediated hydrolysis of mRNA. asODNs have proven effective in gene silencing in many experimental systems, and are being evaluated as treatments for cancer and other diseases in human clinical trials. It was recently reported that the stability of DNA hairpins relative to their corresponding RNA/DNA hybrids influenced the extent of RNA degradation by RNase H. Antisense peptide nucleic acids (PNAs) or DNA oligonucleotides with a morpholine backbone, down-regulate gene expression in many model organisms (such as fish, flies, frogs, chickens, worms, sea urchins) by sterically blocking ribosomal protein synthesis.